As a method for introducing a fluorine atom bonded to a carbon atom into a compound, (a) a method of reacting a fluorinating agent which generates fluorine anions (such as KF or HF) with a chlorine atom bonded to a carbon atom to carry out a nucleophilic substitution reaction of F−. As a method for obtaining a fluorine-containing compound having a geminal difluoro structure by means of said method, a method of fluorinating a compound having a geminal dichloro structure (—CCl2 structure) at the corresponding part as a material may be mentioned.
However, it is generally difficult to selectively obtain a desired compound having a geminal dichloro structure to be used for the reaction of (a), and such a method can hardly be employed as an industrial production method, such being problematic. Particularly, when a ketone part of a compound having a C—H structure at the α-position of a ketone is converted to a geminal dichloro structure, a reaction such as elimination of HCl takes place, whereby at least two types of compounds are formed, and it tends to be difficult to obtain an intended compound with a high yield, such being problematic. Accordingly, a method of converting a ketone to a geminal dichloro structure, followed by fluorination, has not been carried out.
Further, as another method of synthesizing a fluorine-containing compound having a geminal difluoro structure by another method, (b) a method of reacting a carbonyl compound or a thiocarbonyl compound with a fluorinated sulfur type fluorinating agent (hereinafter referred to as SF compound) such as SF4 (J. Ing. Nucl. Chem., 1964, 26, 41.) or diethylaminosulfur trifluoride ((CH3CH2)2NSF3: hereinafter referred to as DAST) (Tetrahedron Lett., 1991, 32, 5963.) has been known. Further, in recent years, a method of employing DAST wherein a substituent on a nitrogen atom is converted (U.S. Pat. No. 6,080,886) has been reported.
However, the SF compound in the method (b) is a compound which requires careful handling, and such a problem that a severe reaction which is difficult to control may occur in the after-treatment has been reported, and application as an industrial production method is difficult, such being problematic. Further, in a case where a reaction is carried out by using the SF compound, removal of HF of the product may take place, whereby a fluoroolefin forms as a by-product, thus decreasing purity of the product. Further, depending upon the substrate used for the reaction, the difference in the boiling point between the fluoroolefin as the by-product and the intended compound is small, whereby a complicated separation operation may be required, or the yield may significantly decrease by the purification operation, such being problematic.
Further, a means to fluorinate a chloroolefin obtained by (c) Diels-Alder reaction with HF has been reported (U.S. Pat. No. 4,792,618). However, compounds to which the method (c) can be applied are limited in structure. Further, in many cases, isomers which are difficult to be separated and purified form as by-products, such being disadvantageous as a method for obtaining a geminal difluoro compound with a high purity.
It is an object of the present invention to overcome the above problems, and to provide a process for synthesizing an intended compound having a geminal difluoro structure with a high yield from a carbonyl compound which is readily available.